An epizootic of mousepox at the National Institute of Health in late 1979 (preceding outbreaks in biomedical research institutions in four other states) caused severe disruptions in research and revealed a serious deficiency in knowledge of the epizootiology and biology of this disease. Since such information is essential to developing effective strategies for prevention and control, epizootiologic studies were commenced (in April of 1980). A computer-based system was developed for the collection and processing of data, which included calculations of prevalence of cases by time, place, mouse strain, etc. Data from the NIH outbreak and outbreaks at other institutions indicated that the virus behaves differently in different inbred strains of mice. At NIH as well as elsewhere, infected mice had been present for several months before recognition, providing potential for extensive spread of the virus. However, virus remained localized within a few cages in a few rooms. Nevertheless, due to misconceptions of the epizootiology of ectromelia virus in inbred mice and nonspecific results from serologic assays, large numbers of mice were unnecessarily destroyed.